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J Clin Endocrinol Metab. 2013 Feb;98(2):E397-402. doi: 10.1210/jc.2012-2779. Epub 2012 Dec 28.

Homozygous leptin receptor mutation due to uniparental disomy of chromosome 1: response to bariatric surgery.

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Institut National de la Santéet de la Recherche Médicale (INSERM), Unité (U)872, Team 7, Nutriomique, Universite´ Pierre et Marie Curie-Paris 6, Centre de Recherche des Cordeliers, 75006 Paris, France.



Severe early-onset obesity with major hyperphagia associated with hypogonadotropic hypogonadism is recognized as the main clinical presentation of leptin (LEP) or LEP receptor (LEPR) gene complete deficiency. In a few reported cases, homozygous mutations have been found in patients from consanguineous families. Care of LEPR-deficient patients is complicated because they cannot benefit from LEP treatment. Furthermore, gastric surgery may not be recommended in such genetic hypothalamic obesity.


We investigated in a morbidly obese patient the genetic origin of his obesity and evaluated the benefit of bariatric surgery in this case.


The patient exhibited severe early-onset obesity with hyperphagia and delayed puberty in a nonobese family. He had clinical and hormonal follow-up from 3 to 26 years of age. Gastroplasty procedures were undertaken when he was 16 and 18 years old. LEPR genetic analysis of the patient and his relatives was performed.


A new homozygous LEPR sequence frameshift, predicted to generate a truncated protein from a premature stop codon in exon 14, was identified in the proband inherited from two paternal copies of chromosome 1 (isodisomy). Vertical ring gastroplasty was sufficient to induce and maintain a 40-kg weight loss into adulthood.


We described the first case of a patient with chromosome 1 uniparental isodisomy revealed by molecular analysis of LEPR. In this case, gastroplasty may be partially effective for weight control as illustrated.

[Indexed for MEDLINE]

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